We will mount a broad, interdisciplinary research program dedicated to exploring basic and clinical aspects of fungi that cause life-threatening, systemic infections in humans. Our activities will be centered on the fungal opportunists, exemplified by species of Candida, Aspergillus, and Mucor. Such organisms are frequently responsible for illness and death among patients with underlying malignant or immunologically mediated diseases. At UCLA, they are especially prevalent among patients with hematologic malignancies and/or recipients of bone marrow transplants (see documentation within the proposal). In addition, we will address important basic and clinical questions relating to two pathogens of restricted geographic distribution, Coccidioides immitis and Histoplasma capsulatum. Our long-term goals, research objectives and the specific methodology we will apply to attain them are described comprehensively in the eleven interrelated proposals that comprise our overall program. We have coordinated the efforts of established scientists in neighboring institutions, and created a collaborative research program around the large and diverse patient population based at UCLA. By so doing, we have insured that anticipated advances in basic mycology, immunology, epidemiology, and immunodiagnosis, and developmental and applied therapeutics will be placed at the service of patients afflicted with severe fungal infections.